1,3-Dianionic annulation of ketones with ketene dithioacetal: a modified route to 3-aryl/cyclopropyl-5-thiomethyl-phenols and 1-(methylthio)-9,10-dihydrophenanthren-3-ols

A simple and efficient base-mediated [3 + 3] cyclization of 1,3-dianionic ketones with 3,3-bis(methylthio)-1-arylprop-2-en-1-ones was developed to afford 3-hydroxy-biaryls, hydroxy-xylenes, and hydroxy-teraryls. Various tri- and tetra-substituted phenols were prepared from different symmetric and asymmetric ketones. The reaction of 2-(bis(methylthio)methylene)-3,4-dihydronaphthalen-1(2H)-ones with different ketones provided 1-(methylthio)-9,10-dihydrophenanthren-3-ols in very good yield. The scope of the reaction was further extended by the synthesis of cyclopropyl-functionalized phenols. One of the compounds was crystallized, and its structure was confirmed using the single-crystal X-ray approach.

The reaction mixture (RM) was allowed to stir for 30 min, then MeI (42 mmol) was added dropwise over 12-15 minutes.The RM was slowly brought up to room temperature (RT) and stirring continued for another 4-8 hours with monitoring by TLC.After completion of the reaction, RM was poured into crushed ice.Most of the 3,3-bis(methylthio)-1-arylprop-2-en-1-ones were precipitated in crushed ice.The precipitate was filtered and washed with ice-cold water and dried overnight inside a vacuum hood.Few 3,3-bis(methylthio)-1-arylprop-2-en-1-ones were not precipitated on crushed ice, which was extracted with ethyl acetate in ice-cooled water, dried with Na 2 SO 4 and concentrated under reduced pressure.The crude mixture was recrystallized with ethyl acetate and n-hexane.

General information on experimental:
Commercially available reagents and solvents from Alfa Aesar, Spectrochem, Sigma Aldrich, Fischer Scientific and TCI Chemicals were used without further purification. 1H and 13 C NMR spectra were recorded on a 400 MHz and 100 MHz NMR spectrometer (Jeol and Bruker instrument) respectively, and CDCl 3 (from Eurisotop) was used as solvent.
Chemical shifts for all the compounds are reported in parts per million (ppm) shifts (δvalue).One singlet at δ 7.26 ppm of 1 H and a triplet at 77.00 ppm of 13 C NMR for CDCl 3 were taken as an internal standard.Signal patterns are mentioned as s, singlet; d, doublet; dd, double doublet; t, triplet; q, quartet; m, multiplet; bs, broad singlet and bm, broad multiplet.The coupling constant (J) for protons are given in hertz (Hz).Infrared (IR) spectra were recorded on a Perkine Elmer AX-1 spectrophotometer and reported in wave number (cm -1 ).HRMS is reported for the peak of (M+H) + using Agilent G6530AA (LC-HRMS-Q-TOF) spectrometer.Reagent-grade solvents were used for extraction and chromatography.The yield of the product was reported as chromatographically isolated pure materials.

Crystal data of product 5h:
Crystal Preparation: The product is a sticky solid at room temperature.To grow the crystal, a highly concentrated (saturated) solution of the compound 5h was prepared by dissolving it in hot methanol.After that, the compound was cooled to room temperature and kept in the fridge for 3 days.After 3 days of cooling small crystals were generated (with minimum exposure of room temperature).

Figure 2 .
Figure 2. Packing structure of 5h in a unit cell.

Table S1 :
Crystallographic data of 5h